Chronic Restraint Stress Induces an Isoform-Specific Regulationon the Neural Cell Adhesion Molecule in the Hippocampus

[摘要] Existing evidence indicates that 21-daysexposure of rats to restraint stress inducesdendritic atrophy in pyramidal cells of thehippocampus. This phenomenon has beenrelated to altered performance in hippocampal-dependentlearning tasks. Prior studies haveshown that hippocampal expression of celladhesion molecules is modified by such stresstreatment, with the neural cell adhesion molecule(NCAM) decreasing and L1 increasing, theirexpression, at both the mRNA and proteinlevels. Given that NCAM comprises severalisoforms, we investigated here whether chronicstress might differentially affect the expressionof the three major isoforms (NCAM-120,NCAM-140, NCAM-180) in the hippocampus.In addition, as glucocorticoids have beenimplicated in the deleterious effects induced bychronic stress, we also evaluated plasmacorticosterone levels and the hippocampalexpression of the corticosteroid mineralocorticoidreceptor (MR) and glucocorticoidreceptor (GR). The results showed that theprotein concentration of the NCAM-140isoform decreased in the hippoampus ofstressed rats. This effect was isoform-specific,because NCAM-120 and NCAM-180 levels werenot significantly modified. In addition, whereasbasal levels of plasma corticosterone tended tobe increased, MR and GR concentrations werenot significantly altered. Although possiblechanges in NCAM-120, NCAM-180 andcorticosteroid receptors at earlier time points ofthe stress period cannot be ignored; this studysuggests that a down-regulation of NCAM-140might be implicated in the structuralalterations consistently shown to be induced inthe hippocampus by chronic stress exposure. AsNCAM-140 is involved in cell-cell adhesion andneurite outgrowth, these findings suggest thatthis molecule might be one of the molecularmechanisms involved in the complex interactionsamong neurodegeneration-related events.

[学科分类] 精神健康和精神病学